Adrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal cortex with a poor 5-year survival rate of 10-20%. Many ACC patients have no symptoms until their tumors reach a large size. Currently, there is no reasonably sensitive or specific way to distinguish ACC from the much more common benign adenomas. Right now, diagnosis is made on the basis of tumor size and histopathological features that can be summarized by the Weiss score. Weiss scores of 0 or 1 are considered benign, 2 and 3 are ambiguous, and 4 or larger are cancerous. Histological diagnosis of ACC is difficult to make, which makes treatment decisions complicated. It is evident from gene expression profiling studies that some subset of tumors classified as adenomas turn out to be transcriptionally more similar to ACC. Local recurrence is not sufficient to establish the diagnosis of ACC either. Metastatic disease or invasion into a contiguous structure is the only absolute indicator of malignant disease in masses of the adrenal cortex. In addition to the challenges to the cancer diagnosis, there is a lack of clinical studies to guide therapy. Current therapy is often ineffective and may also be associated with intolerable side effects. Outside of CT or PET scanning, there is no way to evaluate whether treatment is working in reducing tumor burden. Therefore, there is a need to develop a test based on a molecular abnormality in ACC that can be used for identification and quantification of circulating tumor cells at an early stage of the cancer.